SUMMARY
# Blood Biomarker vs Tau PET for Treatment Monitoring
## Background and Rationale
# Blood Biomarker vs Tau PET for Treatment Monitoring
Amyotrophic lateral sclerosis (ALS) represents a rapidly progressive neurodegenerative disorder characterized by selective loss of motor neurons, leading to paralysis and eventual respiratory failure. While tau pathology has emerged as a potential contributor to neurodegeneration in ALS, current clinical assessment of anti-tau therapeutic efficacy relies heavil
METHODOLOGY NOTES
**Phase 1: Participant Recruitment and Baseline Assessment (Weeks 0-4)**
• Recruit 120 participants with mild-to-moderate ALS (ALSFRS-R score 20-40)
• Obtain informed consent and collect demographic data
• Perform baseline tau PET imaging using [18F]MK-6240 tracer
• Collect baseline blood samples (10mL EDTA tubes) for biomarker analysis
• Conduct baseline neuropsychological assessment (MMSE, CDR-SB)
• Randomize participants 1:1 to active anti-tau therapy vs placebo
**Phase 2: Treatment Initiation and Early Monitoring (Weeks 4-12)**
• Administer monthly intravenous anti-tau monoclonal antibody (15mg/kg) or placebo
• Collect blood samples at weeks 6, 8, 10, and 12 for biomarker monitoring
• Measure plasma p-tau217, p-tau181, NfL, and GFAP using Quanterix Simoa platform
• Perform safety assessments and adverse event monitoring
• Conduct interim neurological evaluations (ALSFRS-R, muscle strength testing)
**Phase 3: Mid-Treatment Assessment (Weeks 12-16)**
• Perform second tau PET scan a